cetugex™: phase 1 study in cancer patients

Conditions: Solid Tumors

Summary: this was a prospective, open label, multicenter study evaluating the safety, tolerability and pharmacokinetics of cetugex™ after intravenous administration in patients with egfr positive, locally advanced and/or metastatic solid cancers. the effect of cetugex™ on the development of anti-drug antibodies and on tumour response was also evaluated.

male or female patients ≥18 years of age with a histologically confirmed locally advanced and/or metastatic solid organ tumor. patients enrolled in germany were required to have a positive egfr overexpression status. patients must have experienced a failure or non-availability of standard therapy (had received at least one line of chemotherapy and further standard therapy was not an option at study entry). open-label, non-randomized, inter-patient dose-escalation, multi-center study. patients were to receive cetugex until disease progression or until intolerable toxicities occurred.

Eligibility criteria:
inclusion criteria: 1. male or female and age ≥ 18 yrs 2. histologically confirmed egfr positive locally advanced and/or metastatic solid organ tumour 3. measurable or non-measurable tumour 4. failure of standard therapy or non-availability of standard therapy (patients must have received at least 1 line of chemotherapy and further standard therapy is not an option at study entry) 5. all anti-tumour therapies must be completed 4 weeks before start of study treatment; treatment with cetuximab must be completed at least 6 weeks prior to study start 6. ecog performance status ≤1 and estimated life expectancy of ≥ 3 months 7. adequate organ function: * bone marrow function: hemoglobin ≥ 100 g/l; white blood cell count (wbc) ≥ 3.0 x 10\^9/l; absolute neutrophil count (anc) ≥ 1.5 x 10\^9/l; platelet count ≥ 100 x 10\^9/l * hepatic: aspartate aminotransferase (asat) and alanine aminotransferase (alat) ≤ 2.5 times upper limit of normal (uln) (≤ 5 x uln if hepatic metastases present); bilirubin ≤ 1.5 x uln; alkaline phosphatase ≤ 5.0 x upper limit of normal (uln) * renal: creatinine \< 1.5 x uln 8. patients of both genders with procreative potential must use effective contraception while enrolled in the study and for at least 4 weeks after the last study drug infusion 9. written informed consent must be obtained prior to conducting any study-specific procedures for expansion phase only: 10. no prior treatment with cetuximab allowed exclusion criteria: 1. chemotherapy, radiation, other anti-cancer therapies including any investigational agents at the study enrolment within 4 weeks prior to study enrolment 2. concurrent anti-tumour therapy or concurrent immunotherapy 3. concurrent systemic steroids except topical (inhaled, topical, nasal) or replacement therapy for the last 28 days. 4. major surgery within 4 weeks prior entering the study and/or incomplete recovery from surgery or planned major surgery 5. primary or secondary immune deficiency 6. clinically active infections \> ctcae grade 2 7. prior allergic reaction to a monoclonal antibody (e.g. trastuzumab, cetuximab or bevacizumab). 8. active hepatitis b assessed by serology, hepatitis c by histology; human immunodeficiency virus (hiv) seropositivity 9. any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. patients with a previous malignancy but without evidence of disease for ≥ 3 years will be allowed to enter the study. 10. uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cava-syndrome, chronic symptomatic respiratory disease. 11. clinical signs of brain metastasis or leptomeningeal involvement 12. symptomatic congestive heart failure (new york heart association \[nyha\] 3 or 4); unstable angina pectoris within 6 months prior to enrollment; significant cardiac arrhythmia, or history of stroke or transient ischemic attack within 1 year. 13. active drug abuse or chronic alcoholism 14. pregnancy or breastfeeding

Keywords: advanced solid cancers metastatic solid cancers